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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2017  |  Volume : 28  |  Issue : 6  |  Page : 1427-1431
Familial hemolytic uremic syndrome with occurrence in the postpartum period


1 Mother Teresa University Hospital Center, Tirana, Albania
2 Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia

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Date of Web Publication18-Dec-2017
 

   Abstract 


The hemolytic uremic syndrome (HUS) is a heterogeneous group of similar entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure (ARF) and is an important cause of ARF in childhood. Mutations have been reported in the complement regulatory protein factor H in both sporadic and familial HUS and have been identified in 10–20% of cases. Inherited HUS is unusual. We report the occurrence of HUS in two siblings after delivery, complicated with ARF and with a good outcome.

How to cite this article:
Barbullushi M, Idrizi A, Spasovski G. Familial hemolytic uremic syndrome with occurrence in the postpartum period. Saudi J Kidney Dis Transpl 2017;28:1427-31

How to cite this URL:
Barbullushi M, Idrizi A, Spasovski G. Familial hemolytic uremic syndrome with occurrence in the postpartum period. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Dec 11];28:1427-31. Available from: http://www.sjkdt.org/text.asp?2017/28/6/1427/220859



   Introduction Top


The hemolytic uremic syndrome (HUS) is a heterogeneous group of similar entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure (ARF). HUS constitutes an important cause of ARF in childhood.[1]

The overall incidence of D+ HUS is estimated to be approximately 2.1 cases per 100,000 persons per year, with a peak incidence in children who are younger than five years (6.1 cases per 100,000 per year). The lowest rate is in adults aged 50–59 years (0.5 cases per 100,000 per year).[2]

Familial occurrence of HUS is reported in siblings[3],[4],[5],[6] in a few families with autosomal dominant inheritance[7],[8],[9] and rarely with autosomal recessive transmission.[4] Mutations have been reported in the complement regulatory protein factor H in both sporadic and familial HUS[10],[11],[12],[13] in 10%–20% of cases studied. Post-partum HUS is a rare syndrome and has a poor outcome. We report the occurrence of HUS in two siblings who had postpartum HUS, complicated by ARF with a good outcome. Details about the first case have been published earlier.[14]


   Case Reports Top


Case 1

A 28-year-old female was diagnosed as having postpartum HUS in August 1990 after pregnancy and delivery,[14] and her data are showed in [Table 1].
Table 1. Laboratory data at the onset of the two episodes of hemolytic uremic syndrome in the first
patient.


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The diagnosis was confirmed by renal biopsy: the presence of crescent formation with fibrinfibrinogen in the glomeruli in addition to the luminal narrowing of arterioles. Deposits of IgM were observed in the glomeruli on immunofluorescence. Daily treatment was instituted with 100 mg aspirin, 25 mg dipyridamole, 50 mg prednisolone i.v. and fresh plasma exchange (PE). The treatment with PE consisted of exchange of 1.5 L plasma volume (60–75 mL/ kg) per session, through a percutaneous dual lumen central venous femoral catheter with blood flow rate of 80–100 mL/min (four sessions in total); once she became anuric, she was put on dialysis for 19 days and subsequently discharged from the hospital in a good condition, with complete recovery of renal function and normalization of all biochemical parameters.[14] Three years later, the patient presented again at our department after her second pregnancy [Table 1]. Because of the problems after the first delivery, the patient was kept under strict nephrological control during her second pregnancy, and she had an uneventful antenatal period and full-term normal delivery. She again developed features suggestive of postpartum HUS which was managed in a manner similar to the first episode. In this episode, we did not perform a renal biopsy. She made complete recovery and the blood pressure, renal, liver, and neurological examinations also remained normal.

The workup at our department including clinical examination, laboratory investigations, and the clinical course were consistent with the diagnosis of postpartum HUS. A couple of alternative diagnoses were very carefully excluded in this case by appropriate investigations. She required dialysis again since she became anuric and started slowly recovering thereafter.[14]

Unfortunately, 10 years after the second episode of HUS, the patient went into terminal renal failure requiring chronic hemodialysis (HD) treatment, with a persistent resistant hypertension that became uncontrollable even on treatment with at least five antihypertensive medicaments. After more than five years on HD, she had a stroke following which she has residual neurologic sequelae.

Case 2

The first patient’s daughter, a 26-year-old woman, presented with severe renal failure to the Nephrology Department immediately after her first delivery. She had anuria, anemia, and moderate thrombocytopenia. A diagnosis of HUS was made. PE was started and substitution performed with fresh frozen plasma; exchange of 1 L plasma (60 mL/kg) per session through a percutaneous dual lumen femoral venous catheter with blood flow rate of 100 mL/min and a total of three sessions were performed. Intravenous hydrocortisone (250 mg) was administered. After about 15 days from the beginning of the illness, signs of active hemolysis disappeared, and renal function had partially improved. The C3 serum level was low. The patient refused to undergo a renal biopsy.

After the episode of the first patient’ s daughter, we performed a genetic study, which became available at our university. It demonstrated the absence of HF1 and MCP mutations but a polymorphic variant of the HF1 gene (C-257T promoter region). Importantly, this polymorphism was found to be strongly associated with the nondiarrhea-HUS, as presented in both cases.


   Discussion Top


These cases present two interesting features. First, two episodes of postpartum HUS have not been previously reported to the best of our knowledge. Second, the mother and her daughter were found to have very low serum levels (5% of normal) of factor H, a regulatory protein of the alternate complement pathway. Both patients had low levels of serum C3, factor B, reflecting persistent alternate pathway activation. Although crescentic glomerular lesions are uncommon in HUS, the histologic findings of our first case revealed the presence of crescentic formation with fibrin-fibrinogen in glomeruli and vessels, associated also with low serum levels of C3.

The first case is also interesting with regard to the good outcome of postpartum HUS with a complete remission and return of renal function toward normal, knowing that postpartum HUS is associated with a poor prognosis in general.[15] In fact, the two episodes of the first patient showed complete recovery of renal function, i.e., she experienced a complete clinical remission between the two episodes. Moreover, the outcome of the second episode, which we were considering may be fatal, turned out to be even better than the first one.

The apparent improvement in survival in recent years is due to an earlier diagnosis, better management of hypertension, and early institution of dialysis.[16],[17],[18] However, controlled prospective trials with adequate numbers of patients are necessary to evaluate the effects of the proposed therapeutic approaches in the adult patient with severe vascular involvement.[19] The disease may not manifest until middle age, suggesting that a trigger (such as infection or pregnancy), hypothesized as an endothelial cell insult, is required to initiate the disease in individuals unable to control complement activation.[20]

Pregnancy is a frequent triggering event in women.[21],[22],[23] About 20% of women with HUS experience the disease mostly in the initial stages of pregnancy and 80% during the postpartum period.[23] In earlier reports, most women died, or survived with severely impaired renal function, or progressed to ESRD.[24] Complete recovery of renal function occurred in <10% of the patients.[25] However, some cases of HUS with a good outcome have been reported.[26],[27] HUS has been described with increasing frequency by a number of authors as postpartum malignant nephrosclerosis,[28] irreversible postpartum renal failure,[24] accelerated postpartum nephrosclerosis[28], late postpartum intravascular coagulation,[29] and postpartum renal failure.[30] In this regard, our first patient developed terminal renal failure 10 years after her second episode of HUS requiring chronic HD treatment.


   Conclusion Top


Within the involved family, factor H deficiency appeared to be associated with HUS, which is transmitted as an autosomal recessive trait. Persistent C3 hypocomplementemia in the setting of familial and/or recurrent HUS should be a clue to a possible inherited complement deficiency. Although postpartum HUS is quite a rare syndrome and has a poor outcome, a prompt diagnosis and efficient therapy with the existing armamentarium could save lives without unfavorable clinical consequences. The excellent outcome of these patients seems to corroborate this concept.

Conflict of interest: None declared.



 
   References Top

1.
Meyers KE, Kaplan BS. Chapter 50 – Hemolytic-Uremic Syndromes. In: Barratt TM, Avner ED, Harmon WE, editors. Pediatric Nephrology. 4thed. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 811-22.  Back to cited text no. 1
    
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Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035-50.  Back to cited text no. 2
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3.
Kaplan BS, Chesney RW, Drummond KN. Hemolytic uremic syndrome in families. N Engl J Med 1975;292:1090-3.  Back to cited text no. 3
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4.
Thompson RA, Winterborn MH. Hypocomple-menaemia due to a genetic deficiency of B1H globulin. Clin Exp Immunol 1981;46:110-9.  Back to cited text no. 4
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5.
Pirson Y, Lefebvre C, Arnout C, van Ypersele de Strihou C. Hemolytic uremic syndrome in three adult siblings: A familial study and evolution. Clin Nephrol 1987;28:250-5.  Back to cited text no. 5
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6.
Pichette V, Quérin S, Schürch W, et al. Familial hemolytic-uremic syndrome and homozygous factor H deficiency. Am J Kidney Dis 1994;24:936-41.  Back to cited text no. 6
    
7.
Farr MJ, Roberts S, Morley AR, Dewar DF, Uldall PR. The haemolytic uraemic syndrome – A family study. Q J Med 1975;44:161-88.  Back to cited text no. 7
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8.
Edelstein AD, Tucks S. Familial hemolytic uraemic syndrome. Arch Dis Child 1978;53: 255-6.  Back to cited text no. 8
    
9.
Warwicker P, Goodship TH, Donne RL, et al. Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int 1998; 53:836-44.  Back to cited text no. 9
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10.
Ying L, Katz Y, Schlesinger M, et al. Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 1999;65:1538-46.  Back to cited text no. 10
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11.
Richards A, Buddles MR, Donne RL, et al. Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition. Am J Hum Genet 2001;68:485-90.  Back to cited text no. 11
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12.
Pérez-Caballero D, González-Rubio C, Gallardo ME, et al. Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome. Am J Hum Genet 2001;68:478-84.  Back to cited text no. 12
    
13.
Caprioli J, Bettinaglio P, Zipfel PF, et al. The molecular basis of familial hemolytic uremic syndrome: Mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol 2001;12:297-307.  Back to cited text no. 13
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14.
Barbullushi M, Thereska N, Idrizi A, Bakalli V. Post-partum HUS: Study of a case with 2 episodes after two normal pregnacies and a good prognosis. J Nephrol 1996;9:27-9.  Back to cited text no. 14
    
15.
Churg J, Goldstein MH, Bernstein J. Thrombotic microangiopathy including hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and postpartum renal failure. In: Tisher CC, Brener BM, editors. Renal Pathology with Clinical and Functional Correlations. Lippincott Company; 1989. p. 1091.  Back to cited text no. 15
    
16.
Remuzzi G, Bertani T. Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and acute cortical necrosis. In: Schrier RW, Gottschalk CW, editors. Diseases of the Kidney. 4th ed. Boston: Little, Brown and Co.; 1988. p. 2301.  Back to cited text no. 16
    
17.
Misiani R, Appiani AC, Edefonti A, et al. Haemolytic uraemic syndrome: Therapeutic effect of plasma infusion. Br Med J (Clin Res Ed) 1982;285:1304-6.  Back to cited text no. 17
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18.
de Jong M, Monnens L. Haemolytic-uraemic syndrome: A 10-year follow-up study of 73 patients. Nephrol Dial Transplant 1988;3:379-82.  Back to cited text no. 18
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19.
Ramos A, Carvalho F. Recovery of renal function in a patient with haemolytic-uraemic syndrome and severe renal involvement. Nephrol Dial Transplant 1993;8:786-7.  Back to cited text no. 19
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20.
Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011;6:60.  Back to cited text no. 20
    
21.
Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010;5:1844-59.  Back to cited text no. 21
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22.
Noris M, Remuzzi G. Atypical hemolyticuremic syndrome. N Engl J Med 2009;361: 1676-87.  Back to cited text no. 22
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23.
Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010;21:859-67.  Back to cited text no. 23
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24.
Robson JS, Martin AM, Ruckley V, Macdonald MK. Irreversible post-partum renal failure. A new syndrome. Q J Med 1968;37:423-35.  Back to cited text no. 24
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25.
Segonds A, Louradour N, Suc JM, Orfila C. Postpartum hemolytic uremic syndrome: A study of three cases with a review of the literature. Clin Nephrol 1979;12:229-42.  Back to cited text no. 25
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26.
Morel-Maroger L, Kanfer A, Solez K, Sraer JD, Richet G. Prognostic importance of vascular lesions in acute renal failure with microangiopathic hemolytic anemia (hemolytic-uremic syndrome): Clinicopathologic study in 20 adults. Kidney Int 1979;15:548-58.  Back to cited text no. 26
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27.
Michael H, Hymphreys, Alfrey AC. Vascular disease of the kidney. In: Brenner BM, Rector FC, editors. The Kidney 3rd ed 1986. p. 1185.  Back to cited text no. 27
    
28.
Wagoner RD, Holley KE, Johnson WJ. Accelerated nephrosclerosis and postpartum acute renal failure in normotensive patients. Ann Intern Med 1968;69:237-48.  Back to cited text no. 28
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29.
Erez O, Mastrolia SA, Thachil J. Disseminated intravascular coagulation in pregnancy: Insights in pathophysiology, diagnosis and management. Am J Obstet Gynecol 2015;213: 452-63.  Back to cited text no. 29
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30.
George JN, Nester CM, McIntosh JJ. Syndromes of thrombotic microangiopathy associated with pregnancy. Hematology Am Soc Hematol Educ Program 2015;2015:644-8.  Back to cited text no. 30
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Correspondence Address:
Myftar Barbullushi
Service of Nephrology, Mother Teresa University Hospital Center, Tirana
Albania
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DOI: 10.4103/1319-2442.220859

PMID: 29265059

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